Abstract Background/Aims The temporal dynamics of biomarkers in anti-cyclic citrullinated peptide antibody (anti-CCP Ab) positive individuals prior to the development of inflammatory arthritis (IA), remain poorly understood. The objectives were to characterise longitudinal biomarker changes in anti-CCP positive at risk individuals and identify those predictive of IA onset within six months (imminent IA). Methods A single-centre, prospective study included 543 anti-CCP positive at risk individuals with new musculoskeletal symptoms but no clinical IA. Participants were followed until IA development. Independent and paired analyses assessed biomarker trajectories, and multivariable panel logistic regression identified predictors of imminent IA. Results Overall, 176/543 (32.4%) participants developed IA (median: 12.1 months IQR 4.5-35.4). The imminent phase was characterised by a significant within-person increase in early morning stiffness (EMS) duration and in the emergence of ultrasound power Doppler (US-PD) signal. A trend of an increase was found in small joint tenderness, rheumatoid factor (RF) levels, and reported pain and disability. Many other biomarkers were consistently higher in those who developed IA but did not increase in the imminent phase. At IA diagnosis, a further increase in biomarkers such as EMS duration, joint tenderness, patient reported outcomes, and erythrocyte sedimentation rate value was identified (Table 1). In the group that did not develop IA, only an early decrease in anti-CCP Ab levels that was observed early in follow-up, ≥ 24 months prior to the final study visit without IA. Using biomarker data from any visit, multivariable analysis identified four independent predictors of IA development within six months: anti-CCP Ab ≥ 3× ULN (OR 13.1, p = 0.022), RF positivity (OR 5.7, p = 0.028), EMS ≥30 minutes (OR 6.5, p = 0.013), and ≥1 tender small joint (OR 7.1, p = 0.010). Individuals with all four risk markers present had a 42.3% probability of developing IA within six months. When the score was dichotomised at a threshold of ≥ 4 points, the risk of imminent IA increased 33.5-fold. Conclusion These findings show longitudinal biomarker shifts prior to IA development, identifying predictive markers for imminent progression. These findings may inform clinical monitoring and guide early intervention strategies. Disclosure L.M. Duquenne: None. D. Sahin-Eroglu: None. J. Wu: None. J.L. Nam: None. A. Di Matteo: Grants/research support; Articulum. K. Harnden: None. S. Sharrack: Grants/research support; Astra Zeneca. H. Sugden: None. L. Thornton: None. R. Chowdhury: None. L. Garcia-Montoya: None. K. Mankia: Honoraria; Abbvie, Lilly, UCB. Grants/research support; Gilead, Lilly. P. Emery: Consultancies; BMS, Abbvie, MSD, Pfizer, Novartis, Roche. Honoraria; Abbvie, Gilead, Lilly, Novartis. Grants/research support; Abbvie, BMS, Lilly, Samsung.
Duquenne et al. (Wed,) studied this question.